Kang Rujun, Wan Junmei, Arstikaitis Pamela, Takahashi Hideto, Huang Kun, Bailey Aaron O, Thompson James X, Roth Amy F, Drisdel Renaldo C, Mastro Ryan, Green William N, Yates John R, Davis Nicholas G, El-Husseini Alaa
Department of Psychiatry, Brain Research Centre, University of British Columbia, Vancouver V6T 1Z3, British Columbia, Canada.
Nature. 2008 Dec 18;456(7224):904-9. doi: 10.1038/nature07605.
Palmitoylation regulates diverse aspects of neuronal protein trafficking and function. Here a global characterization of rat neural palmitoyl-proteomes identifies most of the known neural palmitoyl proteins-68 in total, plus more than 200 new palmitoyl-protein candidates, with further testing confirming palmitoylation for 21 of these candidates. The new palmitoyl proteins include neurotransmitter receptors, transporters, adhesion molecules, scaffolding proteins, as well as SNAREs and other vesicular trafficking proteins. Of particular interest is the finding of palmitoylation for a brain-specific Cdc42 splice variant. The palmitoylated Cdc42 isoform (Cdc42-palm) differs from the canonical, prenylated form (Cdc42-prenyl), both with regard to localization and function: Cdc42-palm concentrates in dendritic spines and has a special role in inducing these post-synaptic structures. Furthermore, assessing palmitoylation dynamics in drug-induced activity models identifies rapidly induced changes for Cdc42 as well as for other synaptic palmitoyl proteins, suggesting that palmitoylation may participate broadly in the activity-driven changes that shape synapse morphology and function.
棕榈酰化调节神经元蛋白质运输和功能的多个方面。在这里，对大鼠神经棕榈酰化蛋白质组的全面表征鉴定出了大多数已知的神经棕榈酰化蛋白质——总共68种，外加200多种新的棕榈酰化蛋白质候选物，进一步测试证实其中21种候选物存在棕榈酰化。新的棕榈酰化蛋白质包括神经递质受体、转运体、黏附分子、支架蛋白，以及SNARE蛋白和其他囊泡运输蛋白。特别值得关注的是发现了一种脑特异性Cdc42剪接变体的棕榈酰化。棕榈酰化的Cdc42亚型（Cdc42-palm）在定位和功能方面均不同于经典的异戊二烯化形式（Cdc42-prenyl）：Cdc42-palm集中在树突棘中，并在诱导这些突触后结构中发挥特殊作用。此外，在药物诱导的活动模型中评估棕榈酰化动力学，发现Cdc42以及其他突触棕榈酰化蛋白质会迅速发生诱导变化，这表明棕榈酰化可能广泛参与塑造突触形态和功能的活动驱动变化。
